New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase

Abstract

The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc.

Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme

“…As previously demonstrated by our research group (Quagliariello, Armenia, et al, 2016) , temozolomide, and temozolomide associated to hyaluronic acid nanohydrogel of quercetin at 0.5 mg/ml (from 1 up to 200 μM or from 1 up to 1,000 μM of drug for A172 and T98MG cells, respectively). Sensitivity (c) of A172 and T98MG cells treated with 5-Aza-2′-deoxycitine to alkylating agent temozolomide.…”

“…Synthetized HA nanohydrogel (HA hydro) and HA nanohydrogel of quercetin (HA‐hydroQ) show an average hydrodynamic size of 188.5 ± 2.3 and 197.3 ± 3.3 nm, respectively with a poly dispersity index (PI) of 0.11 ± 0.018 and 0.08 ± 0.015 and a zeta potential of −31.5 ± 1.2 mV and −31.3 ± 1.1 mV (Table ). Using HPLC method, as reported in our previous studies (Quagliariello, Iaffaioli, et al, ), we calculated the loading of 0.4 mmol of quercetin/gram of hydrogel (corresponding to 40 μM of quercetin in 1 mg/ml of HA‐hydroQ solution). Furthermore FA‐HA hydroQ showed an average hydrodynamic size similar to the non‐fluorescent nanohydrogel with a mean value of 209.2 ± 3.8 nm with a low PI and always a negative zeta potential (−32 mV), (Table ).…”

“…Quercetin has antihistamine, antiviral, immunomodulatory, and antioxidant properties and recently it has shown antitumor activity, which can induce apoptosis of different tumor cells including leukemic cells, medullary and papillary thyroid cancer, pancreatic tumor, breast cancer, hepatocarcinoma, prostate cancer, and glioblastoma (Pan et al, ; Vidak, Rozman, & Komel, ). Its mechanism of action is principally based on the cell cycle regulation, tyrosine kinase inhibition (Quagliariello, Armenia, et al, ) inhibition of cytokine and interleukin secretion (Quagliariello, Iaffaioli, et al, ), AMPK‐Sclerosis Tuberous Complex (TSC) activation and AKT‐mTOR axis inhibition (Lu et al, ) but the main clinical limitation is based on its low bioavailability due to oxidation in biological environment with a not efficient accumulation in cancer cell cytoplasm (Nam et al, ). On the basis of these limitations it would be useful to develop nanocarriers to enhance quercetin delivery protecting it from the oxidative and enzymatic environment and simultaneously achieving a more specific and controlled release in glioblastoma cells.…”

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

“…New multi-TKIs (pyrazolopyrimidines and derivatives of CLM3) and other therapeutic classes such as inhibitors of aurora kinases, proteasome, kinesin spindle protein, cancer stem cells and histone deacetylases, flavonoids, gene and apoptotic cell death-based therapies have already shown promising results in preclinical studies, and may have a role in advanced TC therapy in the future [26][27][58][59][60][64][65][66][67][68][69][70][71]. No writing assistance was utilized in the production of this manuscript.…”

Flavonoids, Thyroid Iodide Uptake and Thyroid Cancer—A Review

“…The authors have found that quercetin had an anti-inflammatory action and also that the compounds had a synergic cytotoxic effect, thus suggesting the anti-tumor activity of the substances [115]. …”